A retrospective analysis of the usage patterns of antiretroviral drugs : a pharmacoeconomic approach

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A RETROSPECTIVE ANALYSIS OF THE USAGE PATTERNS OF

ANTIRETROVIRAL DRUGS: A PHARMACOECONOMIC APPROACH

Jenine Scheepers B. Pharm

Dissertation submitted for partial fulfilment of the requirements for the degree Magister Pharmaciae in Pharmacy Practice, School of Pharmacy at the Faculty of Health Sciences of

the North-West University, Potchefstroom

Supervisor: Prof. M.S. Lubbe

Co-supervisors: Dr. D.M. Rakumakoe Dr. J. du Plessis

Potchefstroom 2008

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Willing is not enough; we must do.

Johann Wolfgang von Goethe

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Acknowledgements

ACKNOWLEDGEMENTS

I would like to express my sincere appreciation and gratitude to each and every person who have contributed in any way to this dissertation.

- Prof. M.S. Lubbe, in her capacity as supervisor of this dissertation, for her guidance, support and assistance throughout the project.

- Dr. D.M Rakumakoe, in her capacity as co-supervisor of this dissertation, for her assistance, insight, time and support.

Dr. J. du Plessis, in her capacity as co-supervisor of this dissertation, for her assistance, feedback, time and support.

- Prof. J.H.P. Serfontein, for his unwavering patience, humour and assistance.

- Ms. A. Bekker, for her assistance with the analyses of the data and her genuine interest and support.

- All the staff of the Department of Pharmacy Practice for their kindness and support.

- The North-West University and National Research Foundation for financial support during the course of this study.

- Interpharm Data Systems® for providing the data for this study.

- Mrs. Terblanche for her assistance with language editing of this dissertation.

- My husband, Arie, for his endless support, encouragement, understanding and love.

- My family, especially my mother and sisters, for keeping me in their thoughts and prayers and for their faith in me.

My friends, for their continued interest and motivation. Special mention to Natasha, Nelmarie, Myrna and Anel, as well as David and Andrew.

My fellow M-students, especially Anri, Corlee, Mariet and Wilmarie for their friendship, and support.

- Above all, to my Lord and Saviour for always giving me the strength and means to reach my goals.

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ABSTRACT

TITLE: A retrospective analysis of the usage patterns of antiretroviral drugs: a pharmacoeconomic approach.

KEYWORDS: HIV/AIDS, antiretroviral drugs (ARVs), pharmacoeconomics, drug utilisation review, prevalence and medicine treatment cost.

More people living with HIV/AIDS reside in South Africa than any other country in the world, and the nation faces colossal challenges in broadening its response to the now-mature and widespread HIV epidemic (WHO, 2005:1). According to South Africa's Medical Research Council, HIV/AIDS has now become the single largest cause of death in South Africa (Dorrington et a/., 2001:6) and has triggered a prominent transferral in the pattern of mortality from the elderly to the young, particularly among young women (Dorrington, 2001:4).

The routine treatment of HIV/AIDS with antiretroviral drugs has transformed HIV-infection from an unvaryingly rapidly terminal illness to a somewhat expensive treatable, chronic disease. Triple therapy or highly active antiretroviral therapy (three-drug combinations of ARVs or HAART) in particular have had paramount impacts on HIV-related morbidity and mortality in settings where these drugs are generally accessible. Objectives of ARV treatment are "maximum, durable suppression of viral load, restoration and/or preservation of immune function, improvement of quality of life and reduction of HIV related morbidity and mortality" (Martinson et a/., 2003:236; Martinez et a/., 2007:251; Hellinger, 2006:1; Kumarasamy, 2004:3).

The Joint United Nations Programme on HIV/AIDS (UNAIDS) estimated that a total of 111 827 South Africans were accessing free antiretroviral treatment in the 200 public health sector facilities across 53 districts and a further 60 000 via the private sector by late December 2005 (UNAIDS, 2005:1).

The objective of this study was to review, analyse and interpret the usage and prescribing patterns of antiretroviral drugs in a section of the South African private health care sector for the period 1 January 2005 to 31 December 2006 by utilising a medicine claims database of a pharmacy benefit management company, and to investigate the costs associated with these drugs by performing a quantitative, retrospective drug utilisation review.

It was found that the prevalence as well as the total medicine cost of ARV medicine items had increased during the study period but the average number of ARV medicine items per prescription as well as both the average cost per ARV medicine item and the average cost per ARV prescription decreased during the study period.

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Abstract

Original innovator ARV medicine items and original ARV medicine items with no generic were found to be relatively expensive in comparison with ARV medicine items in general. Conversely, generic ARV medicine items were ascertained to be relatively inexpensive with reference to ARV medicine items in general.

It was perceived that the average cost of ARV medicine items and prescriptions for both genders decreased from 2005 to 2006, while there was an increase in the prevalence of medicine items and prescriptions claimed for both female and male patients. The prevalence and cost of all types of ARV medicine items were found to be higher for female patients in general.

It was also established that the prevalence of patients receiving antiretroviral treatment in the private health care sector peaks at the age of >30 to 244 years, in comparison with the lower age of >25 to 239 years in the public health care sector. ARV medicine items claimed for patients in the age group >35 to 239 years represented the highest percentage of the total medicine cost incurred during both study years for all ARV medicine types.

The majority of ARV medicine items were prescribed by general medical practitioners, and most ARV medicine items were dispensed by community or private institutional pharmacies.

It was determined that combinations of 2NRTI + NNRTI were prescribed with the highest frequency, which is compliant with traditional HAART or 'triple therapy' regimens.

Lastly, it was found that none of the top 20 prescriptions for one, two and six ARV medicine items were compliant with the National Antiretroviral Treatment (ART) Guidelines. The majority of the top 20 prescriptions for three ARV medicine items (92.67 per cent during 2005 and 89.94 per cent during 2006) were compliant with the National ART Guidelines. Finally, less than half of the top 20 prescriptions for four ARV medicine items (49.60 per cent during 2005 and 36.11 per cent during 2006) were compliant with the National ART Guidelines. Only 5.56 per cent and 3.92 per cent of the top 16 prescriptions for five ARV medicine items were compliant with the National ART Guidelines during the two study years respectively.

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OPSOMMING

TITEL: 'n Retrospektiewe ontleding van die gebruikspatrone van antiretrovirale middels: 'n farmako-ekonomiese benadering.

SLEUTELWOORDE: MIV/VIGS, antiretrovirale middels (ARV), farmako-ekonomie, medisyneverbruik evaluering, voorkoms, medisynekoste van behandeling.

In Suid-Afrika is daar meer MIVA/IGS lyers as in enige ander land ter wereld. Reaksies op hierdie gevorderde en omvangryke probleem van die MIVA/IGS epidemie moet steeds verbeter en dit stel besondere groot uitdagings aan die land en sy mense (WHO, 2005:1). Volgens die Suid-Afrikaanse Mediese Navorsingsraad, het MIVA/IGS nou die grootste enkele oorsaak van dood in Suid-Afrika geword (Dorrington et a/., 2001:6) en het ook 'n prominente uitwerking op die dodetalpatrone van oud en jonk uitgeoefen, veral met betrekking tot die sterftesyfers van jong vroulikes (Dorrington, 2001:4).

Roetinebehandeling vir MIVA/IGS met antiretrovirale middels het MIV infeksie omgeswaai sodat dit van 'n onvermydelik dodelike siekte na 'n chroniese siekte verander het wat teen redelike hoe onkostes behandel kan word. Drieledige terapie of hoogs aktiewe antiretrovirale terapie (drie-middel kombinasies of HAART) het in die besonder 'n uiters belangrike invloed op MIV verwante morbiditeit en mortaliteit uitgeoefen, veral in omgewings waar groter toeganklikheid tot sulke geneesmiddels bestaan.

Doelwitte van antiretrovirale behandeling het te make met die maksimum standhoudende onderdrukking van virale lading, herstel en/of behoud van immuniteitsfunksies, verbetering van lewenskwaliteit en bekamping van morbiditeit en mortaliteit wat met MIV verband hou (Martinson et a/., 2003:236; Hellinger, 2006:1; Kumarasamy, 2004:3).

Volgens 'n skatting (getalle soos vir laat Desember 2005) van die 'Joint United Nations Programme on HIV/AIDS (UNAIDS)' [Gesamentlike Verenigde Volke Program vir MIVA/IGS] het 'n totaal van 111 827 Suid-Afrikaners in die 200 publieke gesondheidsorgeenhede van 53 streke gratis antiretrovirale behandeling ontvang en 'n verdere 60 000 deur middel van die privaat sektor (UNAIDS, 2005:1).

Die doelstelling met hierdie studie was om op analitiese en interpreterende wyse ondersoek in te stel na antiretrovirale middels met betrekking tot die gebruikspatrone, voorskryfpatrone en onkostes daarvan. Die fokus was op 'n geselekteerde deel van die privaat gesondheidsorgsektor in Suid-Afrika vir die tydperk 1 Januarie 2005 tot 31 Desember 2006. Die medisyne eise databasis van 'n firma vir die apteekvoordelebestuursmaatskappy is

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Opsomming

gebruik om data te verkry. Om die gepaardgaande medisyneko^tes van die middels na te gaan, is 'n kwantitatiewe, retrospektiewe medisyneverbruiksevaluering uitgevoer.

Bevindings dui daarop dat beide die voorkoms en die medisynekostes van antiretrovirale middels tydens die studietydperk gestyg het, maar dat die gemiddelde hoeveelheid antiretrovirale middels per voorskrif sowel as beide die gemiddelde koste per antiretrovirale middel en antiretrovirale voorskrif afgeneem het gedurende die studieperiode.

Oorspronklike innoveerder antiretrovirale medisyne items en ook die hiervan sonder 'n generiese ekwivalent, het as relatief duur medisyne items uitgewys, veral in vergelyking met antiretrovirale middels in die algemeen. Daarteenoor is bevestig dat generiese antiretrovirale middels, in vergelyking met antiretrovirale middels in die algemeen, as relatief goedkoop medisyne items vertoon.

Vir beide die manlike en vroulike geslagte het die gemiddelde koste van antiretrovirale middels, sowel as die voorskrifte, volgens waameming tussen 2005 en 2006 afgeneem. Hierteenoor is 'n toename in die voorkoms en die eise wat vir voorskrifte ingedien is gedurende dieselfde tydperk vir albei geslagte waargeneem. Die voorkoms en koste van al die soorte/klasse antiretrovirale middels het geblyk oor die algemeen hoer te wees vir vroulike pasiente.

Die ouderdomsgroep met die meeste pasiente wat antiretrovirale behandeling ontvang het, soos in die privaat gesondheidsorg sektor aangetref, was >30 tot <44 jaar. In vergelyking hiermee is die hoogste punt vir genoemde pasiente in die publieke gesondheidsorg sektor vasgestel op die jonger ouderdomsgroep >25 tot <39 jaar. Eise wat vir antiretrovirale medisyne items ingedien is, het binne die ouderdomsgroep >35 tot <39 jaar die hoogste persentasie van die totale antiretrovirale onkostes vir die twee studiejare getoon.

Die meerderheid van die voorskrifte vir antiretrovirale medisyne items is deur algemene praktisyns gedoen en die meerderheid antiretrovirale voorskrifte is by gemeenskapsapteke of privaat institusionele apteke afgehaal.

Kombinasies wat die meeste hoeveelheid kere voorgeskryf is, was 2NRTI + NNRTI. Dit is in lyn met die tradisionele HAART of 'drieledige terapie' middels.

Daar is bevind dat nie een van die hoogste 20 voorskrifte vir een of twee of ses antiretrovirale medisyne items met die Nasionale antiretrovirale behandelingsriglyne ooreenstem nie. Die meerderheid van die hoogste 20 voorskrifte vir drie antiretrovirale medisyne items (92.67 persent vir 2005 en 89.94 persent vir 2006) het met genoemde riglyne ooreengestem. Minder as die helfte van die hoogste 20 voorskrifte vir vier

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antiretrovirale medisyne items (49.60 persent vir 2005 en 36.11 persent vir 2006) het met die Nasionale antiretrovirale behandelingsriglyne ooreengestem. Slegs 5.56 persent (2005) en 3.92 persent (2006) van die 16 hoogste voorskrifte vir vyf antiretrovirale medisyne items het aan die bepalings van die Nasionale antiretrovirale behandelingsriglyne voldoen.

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Table of Contents

LIST OF TABLES

Table 2.1 AIDS cases reported in South Africa 1982-1991 (Lachman, 1991:65) 7

Table 2.2 Actuarial projection of the epidemic: National summary statistics (ASSA, 2000).... 8

Table 2.3 Estimated annual population growth rates (%), 2001 to 2006 (Statistics South

Africa, 2006:6) 10

Table 2.4 Probability of HIV-1 infection per exposure (Barnett and Whiteside, 2002:38) 23

Table 2.5 Biologic and host-related factors affecting sexual transmission of HIV (Greenblatt &

Hessol, 2000:5) 24

Table 2.6 Symptoms associated with acute HIV infection (Robbins & Walker, 2003:316).... 32

Table 2.7 Antiretroviral medications registered in South Africa (Wilson etal., 2004: 333-334);

(Van Dyk, 2008: 98); (SAHICCS, 2008:20) 40

Table 2.7 (continued) Antiretroviral medications registered in South Africa (Wilson et al.,

2004:333-334); (Van Dyk, 2008: 98); (SAHICCS, 2008:20) 41

Table 2.8 South African National Department of Health regimens for antiretroviral therapy

(South Africa, 2004b:4) 45

Table 2.9 2005 SA HIV Clinicians Society guidelines for commencing antiretroviral therapy

(Gibbon, 2005:306) 49

Table 2.10 HIV-related drugs with overlapping toxicities 51

Table 2.11 Health expenditure in South Africa 2003/4 54

Table 2.12 Categories of HIV/AIDS benefits and benefit management taken from McLeod et

al. (2003:84) (N=77) 66

Table 2.13 Access to ARV therapy for medical scheme beneficiaries from McLeod et al.

(2003:93) 67

Table 4.1 General prescribing patterns for the years 2005 and 2006 79

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Table 4.3 Number of prescriptions per patient per year according to frequency 83

Table 4.4 Prescribing patterns according to type of medicine for the years 2005 and 2006. 84

Table 4.5 Cost prevalence index of ARVs according to type of medicine 86

Table 4.6 Prescribing patterns according to patient gender for the years 2005 and 2006.... 87

Table 4.7 CPI of ARVs in relation to total database according to patient gender 90

Table 4.8 Prescribing patterns according to patient age group for the years 2005 and 2006

for patients in the age group 0 to <4 years 90

for patients in the age group >5 to £9 years 92

for patients in the age group >25 to <29 years 100

for patients the age group >40 to £44 years 106

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List of Tables

for patients in the age group >85 years 124

Table 4.26 Cost-prevalence index of ARVs in relation to total database according to patient

age 126

Table 4.27 Comparison of prevalence of patients receiving ARVs according to patient age

groups for 2004 to 2006 129

Table 4.28 Prescribing patterns according to prescriber for the years 2005 and 2006 for

general medical practitioners 130

Table 4.29 Prescribing patterns according to prescriber for the years 2005 and 2006 for other

practitioners 131

Table 4.30 Prescribing patterns according to prescriber for the years 2005 and 2006 for

pharmacies 133

Table 4.31 CPI of ARV medicine items according to prescriber 134

Table 4.32 Average number of prescriptions per patient per year according to prescriber.. 135

Table 4.33 Prescribing patterns according to provider for the years 2005 and 2006 for

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Table 4.34 Prescribing patterns according to provider for the years 2005 and 2006 for other

practitioners 137

Table 4.35 Prescribing patterns according to provider for the years 2005 and 2006 for

pharmacies 139

Table 4.36 Cost-prevalence index of ARV medicine items according to provider 140

Table 4.37 CPI of ARV medicine items according to prescriber and provider in comparison

with total number of ARV medicine items for 2005 and 2006 140

Table 4.38 Average number of prescriptions per patient per year according to provider 141

Table 4.39 Average cost of original ARV medicine items with no generic for 2005 and 2006

according to patient age group 142

Table 4.40 Average cost of original innovator ARV medicine items for 2005 and 2006

according to patient age group 143

Table 4.41 Average cost of generic ARV medicine items for 2005 and 2006 according to

patient age group 144

Table 4.42 Average cost of ARV medicine items for 2005 and 2006 according to patient

gender 145

Table 4.43 Classification of antiretroviral medicine items (active ingredient and trade names)

in the Top 20 ARV combinations 153

Table 4.44 Top 20 ARV monotherapy according to frequency for 2005 155

Table 4.45 Top 20 ARV monotherapy according to frequency for 2006 157

Table 4.46 Top 20 combinations of 2 ARVs per prescription according to frequency for 2005 160

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List of Tables

Table 4.55 Top 20 ARV monotherapy according to total cost for 2005 181

Table 4.56 Top 20 ARV monotherapy according to total cost for 2006 182

Table 4.57 Top 20 combinations of 2 ARVs per prescription according to total cost for 2005 184

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Table 5.1 ARV combinations ranked number one according to frequency and total cost for

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List of Figures

LIST OF FIGURES

Figure 2.1 Adult HIV management (South Africa, 2004b:1) 43

Figure 2.2 Categorisation of costs and financial limits for HIV/AIDS benefits (McLeod er a/.,

2003:95) 67

Figure 4.1: Schematic classification system of the data as extracted from the database 77

Figure 4.2: Number of ARV prescriptions according to patient gender for 2005 and 2006... 89

Figure 4.3 Total number of ARV medicine items according to type of medicine and patient

age group 147

Figure 4.4 Total number of ARV medicine items according to type of medicine and patient

gender 148

Figure 4.5 Average cost per ARV medicine item according to type of medicine and patient

age group 149

Figure 4.6 Average cost per ARV medicine item according to type of medicine and patient

gender 150

Figure 4.7 Total cost of ARV medicine items according to type of medicine and patient age

group 151

Figure 4.8 Total cost of ARV medicine items according to type of medicine and patient

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CHAPTER 1: INTRODUCTION

1.1 Introduction

The focus of the dissertation is the prescribing patterns of antiretroviral drugs in a section of the private health care sector in South Africa. In this chapter the problem statement, research objectives, and research methodology will be discussed. The chapter will conclude with the division of chapters.

1.2 Problem statement

The Mayo Clinic (2008:1) defines AIDS as "a chronic, life-threatening condition caused by the human immunodeficiency virus (HIV)". HIV disturbs the capability of the human body to successfully combat and prevent infection by disease-causing micro-organisms as it interferes with the functioning of the immune system. This increases susceptibility to a variety of tumours and opportunistic infections that the body would normally withstand, for instance pneumonia and meningitis (Mayo Clinic, 2008:1).

According to the United Nations Aids Reference Group's annual report of 2007, the number of individuals living with HIV worldwide by the end of 2007 was estimated to be 33.2 million (in the range of 30.6-36.1 million) (UNAIDS, 2007:8). In excess of 6 800 persons are newly infected with HIV daily, and over 5 700 people die from AIDS-related causes every day, generally as a consequence of insufficient access to services for HIV treatment and prevention (UNAIDS, 2007:8). South Africa is home to the largest population of individuals living with HIV/AIDS in the world (ljumba et a/., 2004:320), and women aged 15-49 are affected the worst (Statistics South Africa, 2006:3).

Antiretroviral treatment inhibits HIV-1 replication, which alters the natural history of the infection considerably (Wood et a/., 2000:2095), and the correct utilisation of antiretroviral therapies has remarkably reduced HIV-associated mortality over the last several years (Saag, 2003:359). The distribution of protease inhibitors in 1996, the subsequent use of non-nucleoside reverse transcriptase inhibitors in 1998, and more recently the introduction of protease inhibitors boosted with ritonavir have produced valuable treatment possibilities for management of HIV infection (Sabbatani, 2003:476). HIV therapy is constantly evolving and the pharmaceutical industry is progressively developing new antiretroviral drugs (Wilson et a/., 2004:341), but a cure has not been developed yet (Avert, 2008a: 1).

The Declaration of Commitment by the United Nations released by the Office of the United Nations High Commissioner for Human Rights in 2001 (OHCHR, 2001:1) accentuated the fact that all people infected with HIV have the right to treatment. The Declaration also

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Chapter 1: Introduction

observed that the cardinal elements of any effective response to HIV include treatment, care and support (Handford et a/., 2007:2).

Affordabihty has been one of the limitations concerning comprehensive use of ARVs in developing settings (Martinson et a/., 2003:247-248). However, a study by Scholtz (2005:168) showed that the cost of antiretroviral drug therapy in the South African private health care sector decreased from 2002 to 2004. Due to this significant reduction in the prices of patented ARVs in recent years, accessibility has been made possible to people who formerly could not afford them, regardless of private-sector medical scheme cover (McLeod et a/., 2003:92).

Less than 15 per cent of the 47 million citizens of South Africa have medical scheme membership (Anon, 2007:1). As a result the public health care sector is heavily burdened by HIV epidemic, but the private sector is also under a great deal of pressure. Research has indicated that approximately 6 per cent of medical scheme beneficiaries are living with HIV (McLeod et al., 2003:86).

Since the implementation of amendments to the regulations under the Medical Schemes Act (No. 131 of 1998) on 1 January 2005, all medical schemes must provide prescribed minimum benefits to HIV-positive beneficiaries. All beneficiaries now have access to highly active antiretroviral therapy (no less than to the extent provided for the public sector) and all the fundamental monitoring tests (South Africa, 2004a:3-4).

It is clear that further research should be conducted regarding prescribing patterns and utilisation of antiretroviral drugs in the private health care sector of South Africa.

1.3 Research questions

The subsequent research questions can be formulated on account of the preceding discussion:

• How do South African medical aids manage beneficiaries living with HIV/AIDS and what are the associated costs?

• How can HIV/AIDS be conceptualised?

• How can antiretroviral drugs be conceptualised?

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• How do prescribing patterns of antiretroviral agents in the private health care sector reflect in medicine claim databases so that insight may be gained in prescribing practices?

• What are the prescribing patterns of antiretroviral drugs and what are the costs associated with these drugs in the South African private health care sector?

• Does appropriate prescription of combination antiretroviral therapy occur and what are the costs associated with these combinations?

1.4 Research objectives

The research encompasses a general as well as various specific research objectives.

1.4.1 General objective

The objective of this study was to review the usage and prescribing patterns of antiretroviral drugs in a section of the South African private health care sector for the period 2005 to 2006 by utilising a medicine claims database, and to investigate the costs associated with these drugs.

1.4.2 Specific objective

The research project was composed of two phases, a literature review and an empirical investigation. The research objectives of the two respective phases were as follows:

1.4.2.1 Phase 1: Literature review

The specific research objectives of the literature review were:

• To conceptualise the HIV/AIDS pandemic from available literature.

• To describe HIV/AIDS treatment protocols and the antiretroviral drugs involved therein. • To conceptualise from the literature some pharmacoeconomic principles involved in the

South African health care system.

• To study the health care system of South Africa and ascertain through the literature how South African medical aid funds approach and manage antiretroviral therapy.

1.4.2.2 Phase 2: Empirical investigation

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• To determine the usage patterns and cost of drugs in general according to all medicine items and prescriptions in the total medicine claims database for the study period 2005 to 2006.

• To analyse utilisation patterns and cost of antiretroviral agents and antiretroviral prescriptions in the medicine claims database according to gender, age group, prescriber and provider for the two study years.

• To investigate generic substitution of innovator antiretroviral drugs within the two study years.

• To identify combination therapy of antiretroviral drugs and determine the costs associated with these combinations for 2005 and 2006.

1.5 Research method

The research consisted of two phases corresponding to the specific objectives, namely a literature review and an empirical investigation.

1.5.1 Phase 1: Literature review

The following steps were followed in the literature study as contained in Chapter 2:

• Step 1: The HIV/AIDS pandemic. This step of the literature study focuses on the extent of the HIV/AIDS epidemic, the social impact of the epidemic, the transmission of HIV, certain clinical aspects of HIV/AIDS and the stages of HIV disease.

• Step 2: Antiretroviral drugs. This step constitutes the classification and mechanism of action of antiretroviral drugs, treatment protocols for HIV/AIDS, indications for antiretroviral therapy, and drug-drug interactions between antiretroviral agents.

• Step 3: Health care concepts. This step explores the South African health care system, pharmacoeconomic principles and health care concepts, drug utilisation review, and health insurance in South Africa pertaining to HIV/AIDS.

1.5.2 Phase 2: Empirical investigation

The empirical investigation involved several steps which are discussed in-depth in Chapter 3. A retrospective drug utilisation was performed on the antiretroviral medicine items claimed via a pharmacy benefit company for the periods 1 January 2005 to 31 December 2005 and 1 January 2006 to 31 December 2006.

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The study population was selected in accordance with prescriptions analysed on the medicine claims database, and the study focused on the claims data of patients who were prescribed one or more antiretroviral agents during the study period. In order to achieve the objectives of the empirical investigation the innovator and generic forms, prevalence, cost, prescriber and provider of antiretroviral medicine items, as well as patient gender and age were applied as measuring instruments for data analysis.

The data analysis was conducted through the Statistical Analysis System®, SAS 9.1® (SAS Institute Inc., 2003).

The results obtained from the empirical investigation are reported and discussed in Chapter 4. The conclusion, recommendations and limitations derived from the results of the study are discussed in Chapter 5.

1.6 Division of chapters

The division of chapters is as follows:

Chapter 2: HIV/AIDS and antiretroviral treatment protocols in South Africa today

Chapter 3: Empirical investigation

Chapter 4: Results and discussion

Chapter 5: Conclusion and recommendations 1.7 Chapter summary

In this chapter, the problem statement, research questions, research objectives, empirical research method, and division of chapters were explored. HIV/AIDS, antiretroviral drug treatment, and South African health care concepts are discussed in Chapter 2.

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Chapter 2: HIV/AIDS and ART Protocols in SA

CHAPTER

2: HIV/AIDS

AND ANTIRETROVIRAL TREATMENT PROTOCOLS IN SOUTH AFRICA

2.1 Introduction

This chapter focuses on HIV/AIDS disease in a South African context. The magnitude of the epidemic and the resulting impact on different levels of society are reviewed. Different means of transmission of the infection and progression of the disease are examined, and treatment options with antiretroviral drugs are explored. Pharmacoeconomic principles and health care concepts in the South African health care system, especially health insurance, are investigated as pertaining to HIV/AIDS.

2.2 The extent of the HIV/AIDS epidemic in South Africa

South Africa is staggering under the increasingly heavy yoke of HIV-related mortality and disease. The Medical Research Council (Dorrington ef a/., 2001:21) has forecast that the cumulative number of HIV/AIDS deaths will surpass 6 million by 2010. The estimated prediction for 2005 was that HIV/AIDS would be the cause of almost 60.00 per cent of all deaths in South Africa (Martinson ef a/., 2003:236).

The World Health Organization (WHO) states that more people living with HIV/AIDS reside in South Africa than any other country in the world, and the nation faces colossal challenges in broadening its response to the now-mature and widespread HIV epidemic. In all age groups, with the exception of pregnant women over 40 years of age, there has been a continuous increase in prevalence rates, and there has been no indication of a decline in the epidemic. Over the past six years there has been an estimated increase of more than 40.00 per cent in adult deaths in South Africa (WHO, 2005:1). According to South Africa's Medical Research Council, HIV/AIDS has now become the single largest cause of death in South Africa (Dorrington ef a/., 2001:6) and has triggered a prominent transferral in the pattern of mortality from the elderly to the young, particularly among young women (Dorrington ef a/., 2001:4).

2.2.1 Spread of the epidemic

In 1981 the first cases of acquired immunodeficiency syndrome (AIDS) were reported (CDC, 2006:841). Since then, infection with human immunodeficiency virus (HIV) has expanded to pandemic proportions, giving rise to approximately 65 million infections and 25 million deaths. According to the Centers for Disease Control and Prevention (CDC), for the period of 2005 alone, an estimated 2.8 million individuals died from AIDS, 4.1 million new HIV infections occurred, and 38.6 million people were living with HIV (CDC, 2006:841).

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It is currently estimated that South Africa has the largest number of people living with HIV/AIDS worldwide (ljumba et a/., 2004:320). Although estimates differ, it is generally acknowledged that between 4 and 6 million people are infected and that HIV/AIDS is the foremost cause of death in the country (ljumba et a/., 2004:320).

According to Rehle and co-workers new infections with HIV in South Africa occur at a rate of about 1 500 additional infections each day, accounting for about 571 000 newly-infected people in 2005 according to the Human Sciences Research Council (Rehle et a/., 2007:198).

The HIV prevalence rate peaks among women aged 15-49 years. The total prevalence rate of women in this age group is 20.00 per cent. The projected HIV prevalence rate swelled from less than 9.00 per cent in 2005 to 11.00 per cent in 2006 (Statistics South Africa, 2006:3).

The following Table 2.1 illustrates cases of AIDS reported annually in South Africa throughout the eighties at the onset of the epidemic. This demonstrates the enormous escalation of the epidemic when compared to current actuarial projections of the epidemic as exemplified in Table 2.2. The number of patients known to have died is indicated in brackets. Monthly releases show a discrepancy owing to the fact that the disease is not officially notifiable and death figures are in all probability inaccurate.

Table 2.1 AIDS cases reported in South Africa 1982-1991 (Lachman, 1991:65)

Year

Total seen South

African Non-South African 1982 2(2)

_{K D}

1983 4(3) 4(3) 1984 8(8) 8(8) -1985 8(8) 7(7)

_{K D}

1986 24 (23) 14(13) 10(10) 1987 39 (32) 30 (26) 9(6) 1988 88 (54) 82 (50) 6(4) 1989 173(88) 170(87) 3(1) 1990 297 (66) 290(61) 7(5) 1991 79(8) 74(8) 5(?) Total 722 (292) 680 (264) 42 (28)

The progression of the South African epidemic in the 21s t century is further illustrated in

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rise in the total number of people infected with HIV of about 2 341 270 from 2000 to 2008, and an increase of 1 051 616 in AIDS sick. Accumulated AIDS deaths, for the same period of time, is estimated to have risen by 3 418 874 (ASSA, 2000).

Table 2.2 Actuarial projection of the epidemic: National summary statistics (ASSA, 2000)

2000 2007 2008

Numbers (total and infected)

Total population 45 078 805 47 683 822 47 645 665 Total HIV infections 5 263 841 7 695 201 7 605 111

Total births 1 142 387 1 061 205 1 045 853

Births infected perinatally 58 048 71 815 70 748 Babies newly infected by mother's milk 16 259 21 651 21 385 AIDS sick

Total AIDS sick (in the middle of year) 236 228 1 182 710 1 287 844 Deaths

Non-AIDS deaths 387 667 406 824 406 961

AIDS deaths 139 009 664 966 721 915

Accumulated AIDS deaths (to middle of the year) 298 645 3 019 659 3 717 519 Prevalence rates

Antenatal clinics 25.20% 31.70% 31.70%

Women aged 15 - 49 21.50% 29.70% 29.50%

Adult women (ages 20 - 65) 19.60% 26.80% 26.50% Adult men (ages 20 - 65) 20.50% 27.60% 27.20% Adults (ages 20 - 65) 20.10% 27.20% 26.80%

Total population 11.70% 16.10% 16.00%

Incidence rates

Total new infections 892 241 663 514 644 682 Mortality statistics

Life expectancy at birth 56 43 42

Maternal orphan statistics

Total orphans (in middle of the year) 493 860 1 339 615 1 506 386 Total AIDS orphans (in middle of the year) 124 989 1 039 210 1 218 488

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2.2.2 Impact of HIV on society

Unfortunate circumstances including hardship, maltreatment, violent behaviour, bigotry and lack of knowledge help HIV to prosper in communities. Susceptibility to HIV infection and its subsequent influence may be enhanced by unfavourable communal and economic conditions in a society as stated by Lyons (1998:1). In the same manner, HIV/AIDS also instigates and intensifies situations that make it possible for the epidemic to surge. To the same extent that the virus weakens the human body's innate immune defences, it is additionally able to drain family units and the populace of vital resources and social structures essential for productive prevention and care-giving and therapy for HIV/AIDS patients (Lyons, 1998:1).

HIV has a great impact on society, and vice versa. Why do social factors affect HIV/AIDS epidemics? The first explanation is that HIV is transmitted through fundamentally social phenomena, such as sexual and drug injection networks (Friedman et al., 2006:959).

Social standards regarding suitable choice, numbers and timing of sexual partners, and on the subject of acceptable behaviour with those partners, shape essential network variables such as concomitant sexual and drug injection relationships; partner turnover rates; mixing patterns; the size, integration and microstructures of community network components; and the degree of semi-anonymous risk points such as group sex parties, bath-houses, and "shooting galleries" where intravenous drug users convene (Friedman et al., 2006:959).

Sexual and drug-taking behaviours are influenced by social norms, conventions, educational structures and law enforcement practices. Social networks, norms and social support have an effect on how people access, interpret and apply HIV-prevention information and education, the degree to which individuals utilise sexually transmitted disease treatments and HIV therapies, HIV counselling and testing, and affect adherence to therapies. Economic and political conditions and dynamics shape what services are accessible and how problematic, expensive, or stigmatising it is to use them (Friedman et al., 2006:959).

Ultimately, events - like large-scale epidemics - that disturb local or national social networks, communities, services, or social norms, bring about scale migration, or instigate large-scale amalgamation across new sexual or injecting networks, create the potential for risk behaviours or adherence failures that would have formerly been prevented - and these, in turn, might produce epidemic outbreaks (Friedman et al., 2006:959).

Severely afflicted regions will likely be harshly affected by the HIV/AIDS epidemic at multiple levels across the board. Impending outcomes of this pandemic include extensive transformation of demographic patterns, economic decline, volatile social situation, and

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impediment of democracy and authority. Productive adults that are socially and economically valuable are targeted in particular, leading to orphaned children and afflicting sectors of society, government, health care and economy (Manning, 2002:6).

The majority of respondents who participated in a study by Manning (2002:12) stated that "s/tence, denial, and stigma around HIV/AIDS" were the causes of social dilemmas in the district.

The end results of stigma, segregation and prejudice against people living with HIV/AIDS obligate infected individuals to fail to disclose their affliction and to persist with unsafe behaviour that is potentially hazardous to themselves and others (South Africa, 2007a:33). An additional outcome of discrimination against persons infected with HIV/AIDS is denial. Silence and denial regarding HIV and AIDS are equally significant since they inhibit persons from truthfully evaluating their personal risk of infection in addition to gaining access to the extensive variety of existing services concerning HIV/AIDS (South Africa, 2007a:33).

2.2.3 Impact of HIV on population growth

After reviewing projections on population growth, the Bureau for Economic Research (2001:1) concluded that the South African population could grow by merely 1.5 million people between 2000 and 2015 - or 10 million people fewer in contrast to a no-AIDS projection.

Accordingly, Table 2.3, by Statistics South Africa (2006:6), demonstrates that there has been a progressive waning in the implied growth rate for the South African population between 2001 and 2006. The inclusive rate of growth for 2005-2006 is projected at 1.06 per cent with a lower rate for females than males.

Table 2.3 Estimated annual population growth rates (%), 2001 to 2006 (Statistics South Africa, 2006:6)

Estimated annual growth rate (%) for time per od: 2001-2002 2002-2003 2003-2004 2004-2005 2005-2006 Male 1.27 1.24 1.21 1.20 1.09 Female 1.23 1.20 1.16 1.14 1.02 Total 1.25 1.22 1.19 1.17 1.06

2.2.4 Economic impact of HIV

Those regions with a higher prevalence or incidence of HIV infection, like sub-Saharan Africa, is likely to bear the greatest brunt of the economic burden of HIV. Over and above the

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direct costs of treatment and care, the encumbrance related to lost economic productivity as a result of premature morbidity and mortality from HIV is a further critical loss to any society (Beck ef a/., 2001:14).

Worryingly, only 2.00 per cent of those who need treatment on the African continent are receiving it (Ijumba et a/., 2004:332). Several years after UNGASS, antiretroviral therapy (ART) coverage for people in low and middle income countries continues to be exceptionally low, with barely about 400 000 (7.00 per cent) patients accessing ARVs in 2003 out of an estimated 6 million who require treatment.

Ijumba and co-workers (2004:327) specified that reasons indicated as responsible for poor access to ARVs in the developing world and predominantly in sub-Saharan Africa include the following:

• Financial limitations

• Inadequate management systems • Ineffective health systems

• Clinical guidelines that are overly complex or inadequate • Weak laboratory standards

• Defective coordination among players and stakeholders • Stigma and prejudice against people living with HIV/AIDS

2.2.4.1 The influence of poverty and low socio-economic conditions on the spread of HIV.

AIDS and other sexually transmitted diseases are frequently more widespread in countries with lower socio-economic status.

A few explanations citing why low socio-economic conditions advance the spread of sexually transmitted infections are described by Evian (2003:21) as follows:

• The perceived "inferior status" of women leads to sexual exploitation and deterioration of relations between men and women. In several communities, women have almost no control over their sexual lives, and consequentially little means to avert sexually transmitted infections. The situation is often exacerbated by poverty, and this further enhances the spread of sexually transmitted infections.

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• Migrant work and family disruption is a result of high unemployment levels. People are forced to abandon their homes and hence their loved ones, friends, familiar surroundings and local community life. In consequence, migrants often find themselves in lonely, harsh, hostile or estranging surroundings. The ensuing natural need for sex and intimacy results in risky multiple-partner sexual relationships.

• Women often have to turn to prostitution to earn sorely needed money for food and basic needs, and to help raise their children. Young girls may also have transactional sex with older men as a means to earn an income.

• Health care services are often not easily accessible to people in poor living conditions. Therefore, persons with sexually transmitted infections are often not treated and the infections spread more easily.

• Deficient education and low literacy levels contribute to lack of awareness of how to avoid diseases like AIDS. This undermines educational efforts.

• People often abuse alcohol, or turn to drugs as a means of escapism from the reality of everyday hardships. This promotes loss of inhibition and increases the likelihood of sex with multiple partners.

• Family and community life are additionally strained by criminal and violent events that are abundant in urban or poverty-stricken areas.

• Many of the issues depicted above also bring about the collapse of the conventional traditions, customs, values and cultural practices in a society. The norms of accepted sexual conduct and constraints in a community are usually governed by these practices. When these norms are done away with, it often initiates multiple sexual partnerships and indiscriminate sexual behaviour (Evian, 2003:21).

Economic disempowerment can be triggered by poverty and redundancy. Gender vulnerability stems from this economic incapacity and this manipulates choice of sexual conduct and introduction to broader sexual networks. Greater exposure to risk factors such as multiple sexual partners or prostitution, intensify susceptibility to HIV for persons who undertake job hunting, mobile types of employment or migrant labour (South Africa, 2007a:34).

According to the Reports on Mobile Populations and HIV/AIDS by the International Organization for Migration in conjunction with the United Nations Aids Reference Group (IOM-UNAIDS, 2003:8) "mobile types of employment" may refer to informal merchants, sex

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workers, domestic workers, border-traversing labourers, agricultural farm workers, migrant employees (e.g. miners, builders, and militia), long-distance transport drivers, travelling vendors and business travellers, as well as refugees and internally displaced persons.

The prevalence and distribution of the outbreak is essentially influenced by many compelling social, political, structural and economic aspects (Shisana et a/., 2005:xix).

Poverty acts within a socio-epidemiological framework via multiple means as a risk factor for potential HIV infection. It operates by means of various interconnected issues, such as disproportionate income distribution and gender-based economic disparities, or poor governance which leads to deficient public health structure (Piot et a/., 2007:1571-1572).

Elevated vulnerability to HIV transmission has been linked to poverty-related influences. These stressors are the result of the destitute state of affairs in townships, including inadequate and crowded accommodation, as well as unsatisfactory services relating to health and sanitation, transport and food. The situation is further worsened by economic and social issues including unemployment, ineffective education, violence and crime (Kalichman et a/., 2006:1641-1642).

2.2.4.2 Impact of HIV on women

The San Francisco Aids Foundation postulates that presently, virtually half of the 40 million people living with HIV worldwide are represented by women (SFAF, 2006a: 1). Women are affected by AIDS most harshly in areas where heterosexual sex is the prevailing mode of transmission. All the same, women (and men) are additionally at risk of acquiring HIV due to

unprotected sex, prostitution, and injecting drugs with contaminated needles (SFAF, 2006a: 1).

There is a high prevalence of teenage pregnancy in South Africa, yet not enough attention has been called to teenage girls as a target group. The reality that women and girls are more heavily affected by the epidemic than men and boys remains a fundamental concern to the South African National response regarding HIV/AIDS (South Africa, 2007a:35).

The progression and distribution of HIV in women can be affected by an array of gender inequalities. Societal inequalities that women have to cope with can thwart their access to accurate information, quality health care, and suitable emotional assistance pertaining to aspects such as (SFAF, 2006a: 1):

• Child care or guardianship • Food or accommodation

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• Reproductive and gynaecological information and services • Poverty and hardship

• Obtaining providers and organisations that are perceptive of women's needs • Legal concerns, for instance employment, housing, divorce, and child custody • Social and emotional matters, including domestic violence, forced sex, and isolation • Pregnancy and motherhood or single parenting

Unfortunately, South Africa is one of the highest ranking countries pertaining to violence against women worldwide, with more than 53 000 cases of rape reported to law enforcement authorities in 2000, accounting for 123 rapes reported per 100 000 population (South Africa, 2007a:31).

Incidences of sexual assault correlate with a way of life accommodating of violence. It involves destructive mind-sets (for example, premeditated transmission of HIV) and is also associated with the inability to make beneficial choices or to act fittingly in response to HIV prevention campaigns. The occurrence of sexual assault has also been associated with the threat of HIV infection (South Africa, 2007a:31).

An environment is produced for men to have several simultaneous sexual mates and their disinclination to make use of condoms is promoted by inequality over dominance and command in relationships (South Africa, 2007a:32).

Women evidently bear the brunt of the HIV/AIDS epidemic, which should draw attention to the issue of gender vulnerability that necessitates serious contemplation as one of the elements that should be focused on to expand women empowerment and security. Women also routinely shoulder the burden of nursing sick relatives and taking the lead in HIV/AIDS projects in their communities. Taking the high prevalence and incidence of HIV amongst women into consideration, it is crucial that their deep-seated participation in, and derivement of benefits from HIV/AIDS initiatives grow to be a main concern (South Africa, 2007a:35).

2.2.4.3 Impact of HIV on children

A considerable number of South African children are living with HIV and AIDS. A survey conducted by the HSRC (Human Sciences Research Council) in 2005 estimated that there were approximately 129 621 children aged between two and four years and 214 102 children in the age group five to nine years living with HIV or AIDS (Shisana et a/., 2005:142). HIV/AIDS was considered to be responsible for inflating the mortality of children under five years of age in South Africa by 42.00 per cent in 2004. (South Africa, 2007a:37).

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The HIV/AIDS epidemic that is currently ravaging South Africa, will affect all children in one way or the other, and will continue to do so for the foreseeable future. Yet a number of children will be more negatively afflicted than others - predominantly those children who are born HIV-positive or are infected soon after birth (Gow et a/., 2002:4).

Adequate AIDS treatment and care is commonly not accessible to children in view of the fact that existing services are predominantly adult-oriented. There are still significant hurdles concerning the proficiency of personnel in the health care sector and their ability to supervise and care for children with AIDS, in addition to the need for development of suitable pediatric ART formulations (South Africa, 2007a:37).

If access to antiretroviral drugs is lacking, these children will suffer, living only short lives and typically dying in pain. If the children of HIV-positive parents are in good health, they will be adversely affected throughout their parents' illnesses and as a rule be confronted with harsh outcomes once one or both of their parents die (Gow et a/., 2002:4).

Minors (e.g. children younger than 18 years of age) encompass 40.00 per cent of the South African populace. It was approximated in 2004 that about 2.2 million children were orphans (implying that 13.00 per cent of all children under 18 had suffered the loss of either parent). Virtually half of these orphans' parents passed away as a consequence of AIDS (South Africa, 2007a:36; UNAIDS, UNICEF & USAID 2004:7-12, 26).

The children in those families that take in orphans will be adversely affected since fewer resources are on hand for their care and development, since these households often function in very resource constrained circumstances to begin with. Even children coming from unscathed households will be involved as their playmates leave school, through disintegration of their households following death, or suffer the loss of their friends as abandoned children are forced to provide for themselves and relocate away from their homes and villages seeking resources to survive (Gow et al., 2002:4).

Children are subjected to physical, emotional and developmental impediments as a consequence of the epidemic (Gow et a/., 2002:4). Children in severely disadvantaged households are usually affected to the worst degree, and some may be subjected to deficiency pertaining to somatic, material and psychosocial matters. Their health is also under threat due to poverty, parental negligence and absence of nurturing surroundings. These children are frequently removed from guardians and siblings and passed on to reside with other relatives or different caretakers or other social groups (South Africa, 2007a:36).

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Child sexual molestation is also a risk factor for HIV infection in vulnerable children (Kistner et ai, 2004:25). Despite the fact that there is little data on the magnitude of child sexual abuse in South Africa, it may be rather widespread and therefore it is a threat that necessitates enquiry (South Africa, 2007a:37).

2.2.4.4 Impact of HIV on the South African National health care system

The South African Department of Health has set an objective for reduction of HIV infection by 50.00 per cent by 2011 (South Africa, 2007a:10). This programme aims to furnish 80.00 per cent of sufferers and their families with care in a country with the second highest incidence of HIV in the world (South Africa, 2007a: 12).

The hospital sector is undoubtedly the most involved department of the public health sector in the fight against HIV. HIV-related admissions comprised 24.00 per cent of all public hospital admissions and 12.50 per cent of the total public health budget in the year 2000. The cost of both private and public health care sectors' inpatient and ambulatory health care is expected to escalate swiftly (Badri et ai, 2006:48).

Health analysts are hopeful that South Africa is undergoing a basic revision in its official attitude to a disease that by now infects 5.5 million of the nation's 47 million people and takes the lives of an estimated 1 000 South Africans on a daily basis (News24, 2007:1).

By late December 2005, the Joint United Nations Programme on HIV/AIDS (UNAIDS) estimated that a total of 111 827 South Africans were accessing free antiretroviral treatment in the 200 public health sector facilities across 53 districts and a further 60 000 via the private sector. Some 2 369 facilities were also providing voluntary counselling and testing in 2004 (UNAIDS, 2005:1).

The intermingling of weak infrastructure and human capacity limitations are key challenges in intensifying HIV and AIDS programmes. Already overstretched health services being additionally burdened by the AIDS pandemic, have further compounded the capacity predicament (UNAIDS, 2005:1).

In addition, numerous health care professionals are inadequately prepared for providing AIDS care. Comparatively few have been educated regarding the clinical management of the disease, or pertaining to counselling and testing. Professional nurses are responsible for supervision of primary health care facilities, yet the majority are not trained in clinical use of antiretrovirals. Ensuring balance between interventions to provide access to antiretroviral therapy and broader social and economic interventions to assuage poverty and malnutrition, will be one of the key challenges confronting South Africa (Ntuli et ai, 2004:4).

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HIV/AIDS has an impact on the dynamics of provision as well as requirement (e.g. supply and demand) of health care structures. There are dual consequences of HIV on human resources and supply in health systems. HIV/AIDS brings about epidemiological, demand and mortality profiles that quickly shift and vary in patients, which in turn has a negative impact on morale and stress levels in health care workers. Secondly, HIV infection in the actual caregivers is also a challenge (South Africa, 2007a:44).

Extensive use of antiretroviral regimens in more developed countries has significantly diminished AIDS-related morbidity and mortality, and perinatal transmission has been nearly eradicated by the application of antiretroviral prophylaxis among HIV-1-positive pregnant women (Wood et al., 2000:2095).

There has been a considerable decrease in the price of antiretroviral drugs over the past couple of years, largely due to the generic forms of some of these drugs being made available. A number of multinational drug companies that manufacture originator products have also reduced prices and are allegedly selling these antiretroviral drugs at 'no-profit' or 'at a financial loss' in developing countries (Pinheiro et al., 2006:1746).

Valuation of HIV-related health care costs is evolving, basically reflecting the achievements in development of successful prevention and treatment approaches; expanded screening programmes; longer life expectancies of AIDS patients, accessibility of HAART; emergence of viral resistance to HAART, and the shifting demographics of patients newly diagnosed with HIV infection. Infected persons are increasingly those without health insurance (Roberts et al., 2006:877).

Equally as important as even-handedness in the allotment of resources is the need to guarantee that the funds allocated to health are adequate to provide satisfactory levels of health care. The South African Department of Health aims to be treating just over 1 million patients with ART by March 2009 (Cleary et al., 2005:59).

In countries in sub-Saharan Africa, expenditure for therapy and care are lower in absolute terms relative to industrialised countries. However, when expressed as a percentage of resources spent on health care delivery these costs are to be expected to represent a greater liability for developing countries (Beck et al., 2001:14).

A retrospective analysis of the usage patterns of antiretroviral drugs : a pharmacoeconomic approach